Description of fecal shedding of Cryptosporidium parvum oocysts in experimentally challenged dairy calves

The objective was to describe the probability of Cryptosporidium parvum fecal oocyst shedding at different magnitudes of exposure, the pattern of fecal shedding over time, and factors affecting fecal shedding in dairy calves. Within the first 24 h of life, 36 calves were experimentally challenged with C. parvum oocysts at one of four possible magnitudes of oral exposure (1?×?10³, 1?×?10⁴, 1?×?10⁵, and 1?×?10⁶ oocysts), and 7 control calves were sham dosed. Fecal shedding occurred in 33 (91.7 %) experimentally challenged calves and in none of the control calves. There was a difference in the log-total number of oocysts counted per gram of feces dry weight among the four exposure groups; calves with the lowest magnitude of exposure (1?×?10³ oocysts) shed less than the other three groups. At higher magnitudes of exposure, there was more variability in the range of fecal oocyst shedding. There was an inverse relationship between the log-total amount of oocysts counted per gram of feces dry weight and the number of days to the onset of fecal shedding per calf, i.e., the more time that elapsed to the onset of fecal shedding, the fewer oocysts that were shed. The pattern of fecal shedding over time for all calves shedding oocysts was curvilinear; the number of oocysts increased with time, reached a peak, and declined. Therefore, the dynamics of oocyst shedding can be influenced in part by limiting exposure among calves and delaying the onset of fecal oocyst shedding.     

Use of the composite asthma severity index in a pediatric subspecialty clinic

BackgroundThe Composite Asthma Severity Index (CASI) is a comprehensive tool to assess asthma severity, which has been applied in the research setting.ObjectiveTo evaluate, in an outpatient setting, whether a CASI score accurately predicts asthma severity or control as determined by means of subspecialist assessment. Asthma Control Test (ACT) and childhood ACT (C-ACT) scores were generated to provide additional context for CASI scores in relationship to assessments using another clinical tool.MethodsChildren aged 5 to 18 years with a physician diagnosis of persistent asthma were recruited from a tertiary care center. A pediatric pulmonologist made determinations on each participant’s asthma severity and control during a clinic visit. A CASI and ACT/C-ACT score was generated for each patient. Logistic regression and Spearman correlations were used to determine how well CASI scores predicted physician assessments. Agreement between ACT/C-ACT scores and physician assessment of asthma control was determined in supplemental analyses.ResultsCASI scores strongly predicted physician assessment of severity (Spearman correlation = 0.61, P < .001); unadjusted odds ratio (OR) equal to 36.67 (95% confidence interval [CI]: 8.83-152.34); and adjusted OR equal to 32.76 (95% CI: 85.70-188.44). In supplemental analyses, ACT/C-ACT scores strongly predicted physician assessment of control (Spearman correlation = 0.72, P < .001) with an unadjusted OR equal to 42.12 (95% CI: 13.34-133.00) and adjusted OR equal to 55.34 (95% CI: 13.62-224.89).ConclusionUse of the CASI was feasible and accurately predicted physician assessments of asthma severity and control in this sample, which are not distinct entities. The CASI is a robust tool that may be used successfully in ambulatory pediatric asthma care.     

Saturation recovery-prepared magnetic resonance angiography for assessment of left atrial and esophageal anatomy

Objectives:Magnetic resonance angiography (MRA) has been established as an important imaging method in cardiac ablation procedures. In pulmonary vein (PV) isolation procedures, MRA has the potential to minimize the risk of severe complications, such as atrio-esophageal fistula, by providing detailed information on esophageal position relatively to cardiac structures. However, traditional non-gated, first-pass (FP) MRA approaches have several limitations, such as long breath-holds, non-uniform signal intensity throughout the left atrium (LA), and poor esophageal visualization. The aim of this observational study was to validate a respiratory-navigated, ECG-gated (EC), saturation recovery-prepared MRA technique for simultaneous imaging of LA, LA appendage, PVs, esophagus, and adjacent anatomical structures.Methods:Before PVI, 106 consecutive patients with a history of AF underwent either conventional FP-MRA (n = 53 patients) or our new EC-MRA (n = 53 patients). Five quality scores (QS) of LA and esophagus visibility were assessed by two experienced readers. The non-parametric Mann–Whitney U-test was used to compare QS between FP-MRA and EC-MRA groups, and linear regression was applied to assess clinical contributors to image quality.Results:EC-MRA demonstrated significantly better image quality than FP-MRA in every quality category. Esophageal visibility using the new MRA technique was markedly better than with the conventional FP-MRA technique (median 3.5 [IQR 1] vs median 1.0, p < 0.001). In contrast to FP-MRA, overall image quality of EC-MRA was not influenced by heart rate.Conclusion:Our ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality and esophageal visibility than the established non-gated, breath-holding FP-MRA. Image quality of EC-MRA technique has the additional advantage of being unaffected by heart rate.Advances in knowledge:Detailed information of cardiac anatomy has the potential to minimize the risk of severe complications and improve success rates in invasive electrophysiological studies. Our novel ECG-gated, respiratory-navigated, saturation recovery-prepared MRA technique provides significantly better image quality of LA and esophageal structures than the traditional first-pass algorithm. This new MRA technique is robust to arrhythmia (tachycardic, irregular heart rates) frequently observed in AF patients.     

Longevity and Risk Factors of Post Restorations after up to 15 Years: A Practice-based Study

IntroductionThe aims of this multicenter, practice-based cohort study were to evaluate the success and survival of endodontically treated teeth with post restorations (ETT+Ps) and to analyze factors associated with the longevity of ETT+Ps.MethodsEight general dental practitioners each placed up to 27 ETT+Ps without any restriction to post materials or dimensions. Only incisors, canines, and premolars were included. At the last follow-up visit, ETT+Ps were considered as successful if the post and the initially placed definitive restoration were sufficient, whereas ETT+Ps were considered as survived if the post was still in function. Multilevel Cox proportional hazards models were used to evaluate the association between a range of predictors and time until no success and no survival.ResultsOverall, 195 endodontic posts in 195 patients were followed up for a mean (95% confidence interval) of 91 (81–101) months; the longest follow-up was 15 years. Of these, 122 ETT+Ps were considered successful (estimated success time = 110 [101–120] months), and 152 ETT+Ps survived [estimated survival time = 133 [124–141] months). Regarding the categories of success and survival, the annual failure rates were 6.0% and 3.3%, respectively. Recementation of old (telescopic) crowns after placing new posts was the only significant predictor for decreased time until failure for both success and survival analyses. By excluding recemented restorations, annual failure rates decreased to 3.5% and 2.1%, respectively.ConclusionsFor EET+Ps placed in a private practice setting, high success and survival rates were observed. If old (telescopic) crowns were recemented after new posts were placed, the high risk of subsequent failure should be considered and communicated with patients.     

Combined NGS Approaches Identify Mutations in the Intraflagellar Transport Gene IFT140 in Skeletal Ciliopathies with Early Progressive Kidney Disease

Ciliopathies are genetically heterogeneous disorders characterized by variable expressivity and overlaps between different disease entities. This is exemplified by the short rib‐polydactyly syndromes, Jeune, Sensenbrenner, and Mainzer‐Saldino chondrodysplasia syndromes. These three syndromes are frequently caused by mutations in intraflagellar transport (IFT) genes affecting the primary cilia, which play a crucial role in skeletal and chondral development. Here, we identified mutations in IFT140, an IFT complex A gene, in five Jeune asphyxiating thoracic dystrophy (JATD) and two Mainzer‐Saldino syndrome (MSS) families, by screening a cohort of 66 JATD/MSS patients using whole exome sequencing and targeted resequencing of a customized ciliopathy gene panel. We also found an enrichment of rare IFT140 alleles in JATD compared with nonciliopathy diseases, implying putative modifier effects for certain alleles. IFT140 patients presented with mild chest narrowing, but all had end‐stage renal failure under 13 years of age and retinal dystrophy when examined for ocular dysfunction. This is consistent with the severe cystic phenotype of Ift140 conditional knockout mice, and the higher level of Ift140 expression in kidney and retina compared with the skeleton at E15.5 in the mouse. IFT140 is therefore a major cause of cono‐renal syndromes (JATD and MSS). The present study strengthens the rationale for IFT140 screening in skeletal ciliopathy spectrum patients that have kidney disease and/or retinal dystrophy.     

A neural correlate of visceral emotional responses: evidence from fMRI of the thoracic spinal cord

Functional magnetic resonance imaging (fMRI) of thoracic spinal cord neurons was used to examine the neural correlates of visceral emotional responses. Participants completed four spinal fMRI runs involving passive viewing (i.e. no movement) and motoric responses to negative or neutral images. Negative images, particularly in the movement condition, elicited robust activity in motoric nuclei, indicating ‘action preparedness’. These images also enhanced activity in autonomic and sensory nuclei, thus providing a clear neural representation of visceral responses to emotional stimuli.     

Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid–Resistant Nephrotic Syndrome

Background and objectives

Treatment of congenital nephrotic syndrome (CNS) and steroid–resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high–throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease.

Design, setting, participants, & measurements

Cross–sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50–178). Genotyping was performed systematically in all patients.

Results

The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA–induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy.

Conclusions

The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.